No abstract

People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs.

No abstract

No abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an extremely contagious disease whereby the virus damages the host’s respiratory tract via entering through the ACE2 receptor. Cardiovascular disorder is being recognized in the majority of COVID-19 patients; yet, the relationship between SARS-CoV-2 and heart failure has not been established. In the present study, SARS-CoV-2 infection was induced in the monkey model. Thereafter, heart tissue samples were collected, and pathological changes were analyzed in the left ventricular tissue by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to T lymphocytes and macrophages. The findings revealed that SARS-CoV-2 infection induces several pathological changes in the heart, which cause cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells, and hypertrophy. Furthermore, collagen-specific staining showed the development of cardiac fibrosis in the interstitial and perivascular regions in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. These findings suggest the progression of the disease, which can lead to the development of severe complications, including heart failure. Additionally, SARS-CoV-2 antigen staining detected the presence of virus particles in the myocardium. Thus, we found that SARS-CoV-2 infection is characterized by an exaggerated inflammatory immune response in the heart, which possibly contributes to myocardial remodeling and subsequent fibrosis.

Background: Recent reports suggest the presence of the SARS-CoV-2 virus in the myocardium of patients who died from the COVID-19 disease. Cardiovascular injury in COVID-19 patients is an established extra-pulmonary manifestation of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection which may lead to induction of arrhythmia, acute heartfailure, thickening of ventricular wall, reduced ejection fraction and thromboembolism. Non-human primates (NHP) provide a useful model to study cardiovascular changes due to their homology to the ACE2 receptor in humans. Aim: The aim of this study is to characterize the pathological changes in the heart of SARS-CoV-2 infected NHPs. Methods: In the present study, SARS-CoV-2 infected primates via aerosol route (n=4), multi-routes (i.e., oral, nasal, intratracheal and conjunctival) (n=4), and a control group (n=5) were included. Heart tissue samples were collected and the left ventricular tissue was analyzed by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to CD3, CD68 andSARS-CoV-2 nucleocapsid protein. Results: Several pathological findings were observed in the heart, including cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells as well as hypertrophy. Collagen specific staining showed development of cardiac fibrosis in the interstitial as well as in the perivascularregion in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. Additionally, SARS-CoV-2 nucleocapsid protein staining detected the presence of virus particles in the myocardium. Conclusion: COVID19 infection is characterized by exaggerated inflammatory immune response in the heart which possibly contributes to myocardial remodeling and subsequent fibrosis. These findings suggest progression of disease which could lead to development of severe complications including heart failure.

Abstract:The aims of this study were to: 1) compare the effects of speed-based versus heart-rate-based high-intensity interval training (HIIT) on changes in high-intensity intermittent running performance, and 2) examine the between-group differences in heart rate (HR) and rating of perceived exertion (RPE) responses during the training sessions. Sixteen female students were divided into the HR-based (n=8, M±SD, age 17.3±0.2 years, body mass, 59.2±5.7 kg, and body height, 167.8±2.2 cm) and speed-based (n=8, age 17.2±0.3 years, body mass, 57.7±6.4 kg, and body height, 171.0±5.1 cm) groups before commencing the HIIT intervention. After completing five weeks of HIIT, both the HR-based and speed-based groups showed most likely moderate enhancement in high-intensity intermittent running performance (+9%, 90% confidence limits [CL] However, the difference between the experimental groups with regard to changes in high-intensity running performance was trivial. Between-group differences of weekly average HR and RPE responses showed trivial to moderate (ES range; -0.95; 0.15) and moderate to very large (ES: -0.63; -2.88) values, respectively. Although it seems that both the speed-based and HR-based HIIT approaches have some limitations when implementing for HIIT individualization, using the speed reached at the end of the 30-15 Intermittent Fitness test (V IFT ) seems to elicit the same performance enhancement, but with lower psychophysiological responses during short-term interventions.

Background: Despite antiretroviral drugs-mediated control of active HIV infection, cardiovascular disease (CVD) remains one of the leading causes of comorbidity in people living with HIV/AIDS (PLWHA). Recent studies suggest that activation of the immune system and chronic inflammation increases CVD risk in PLWHA. Dysregulation of the immune system can interact with several cellular functions, including autophagy and mitophagy. The autophagic factor Beclin1 is a crucial regulator of cellular autophagy and mitophagy. In this study, we tested the role of Beclin1 in cardiac function using a mice model of HIV. Methods and Results: This study was performed using transgenic mice of HIV-1 Tg26 mice, which was constructed before using HIV-1 DNA with deletion of 3-kb region of the gag/pol genes. Tg26 mice were crossed with Beclin1 transgenic mice to test the role of Beclin1. Cardiac function of Tg26 and Tg26 mice crossed with Beclin1 was evaluated by echocardiography. Cardiac autophagy was determined by western blots using autophagy regulatory markers. Our data suggest that Tg26 mice have significantly reduced cardiac function. Further, Tg26 mice show increased reactive Oxygen species (ROS) level, accumulation of LC3II, increased P62 level, and reduced autophagy flux. Additionally, western blots with cardiac tissue show upregulation of electron transport chain (ETC) complex proteins of mitochondria in the Tg26 mice that may be due to defective mitochondria accumulation in Tg26 mice heart. Interestingly, Beclin1 expression can improve the cardiac function of Tg26 mice heart. Mechanistically, we found that Beclin1 overexpression can restore the autophagy flux and reduce the cellular ROS level in the heart of Tg26 mice. Conclusion: Our study suggests that Beclin1 plays critical role in regulation of cardiac function during HIV induced cardiomyopathy and can be used as a potential therapeutic tool to control comorbidity in the PLWHA.